Variant chr20-2860127-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022575.4(VPS16):c.216C>T(p.Ser72=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,613,888 control chromosomes in the GnomAD database, including 20,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1562 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19394 hom. )

Consequence

VPS16
NM_022575.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.79

Variant links:

Genes affected

VPS16 (HGNC:14584): (VPS16 core subunit of CORVET and HOPS complexes) Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene encodes the human homolog of yeast class C Vps16 protein. The mammalian class C Vps proteins are predominantly associated with late endosomes/lysosomes, and like their yeast counterparts, may mediate vesicle trafficking steps in the endosome/lysosome pathway. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2009]

VPS16 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 20-2860127-C-T is Benign according to our data. Variant chr20-2860127-C-T is described in ClinVar as [Benign]. Clinvar id is 1242073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.79 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS16	NM_022575.4 linkuse as main transcript	c.216C>T	p.Ser72=	synonymous_variant	3/24	ENST00000380445.8	NP_072097.2
VPS16	NM_080413.3 linkuse as main transcript	c.216C>T	p.Ser72=	synonymous_variant	3/20		NP_536338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS16	ENST00000380445.8 linkuse as main transcript	c.216C>T	p.Ser72=	synonymous_variant	3/24	1	NM_022575.4	ENSP00000369810	P1	Q9H269-1
VPS16	ENST00000380469.7 linkuse as main transcript	c.216C>T	p.Ser72=	synonymous_variant	3/20	2		ENSP00000369836		Q9H269-2
VPS16	ENST00000417508.1 linkuse as main transcript	c.15+320C>T		intron_variant		5		ENSP00000409840
VPS16	ENST00000453689.5 linkuse as main transcript	c.15+320C>T		intron_variant		3		ENSP00000417031

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19571

AN:

151994

Hom.:

1560

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0439

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.222

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.119

GnomAD3 exomes

AF:

0.165

AC:

41375

AN:

251244

Hom.:

3867

AF XY:

0.171

AC XY:

23279

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.0391

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.174

Gnomad EAS exome

AF:

0.237

Gnomad SAS exome

AF:

0.266

Gnomad FIN exome

AF:

0.177

Gnomad NFE exome

AF:

0.154

Gnomad OTH exome

AF:

0.167

GnomAD4 exome

AF:

0.157

AC:

228823

AN:

1461774

Hom.:

19394

Cov.:

AF XY:

0.161

AC XY:

116737

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.0413

Gnomad4 AMR exome

AF:

0.118

Gnomad4 ASJ exome

AF:

0.171

Gnomad4 EAS exome

AF:

0.198

Gnomad4 SAS exome

AF:

0.264

Gnomad4 FIN exome

AF:

0.174

Gnomad4 NFE exome

AF:

0.150

Gnomad4 OTH exome

AF:

0.158

GnomAD4 genome

AF:

0.129

AC:

19565

AN:

152114

Hom.:

1562

Cov.:

AF XY:

0.132

AC XY:

9815

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0438

Gnomad4 AMR

AF:

0.125

Gnomad4 ASJ

AF:

0.166

Gnomad4 EAS

AF:

0.222

Gnomad4 SAS

AF:

0.279

Gnomad4 FIN

AF:

0.161

Gnomad4 NFE

AF:

0.156

Gnomad4 OTH

AF:

0.121

Alfa

AF:

0.149

Hom.:

2985

Bravo

AF:

0.116

Asia WGS

AF:

0.256

AC:

888

AN:

3478

EpiCase

AF:

0.156

EpiControl

AF:

0.154

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

3.9

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over